Skip to main content

Full text of "USPTO Patents Application 10561839"

See other formats


BEST AVAILABLE COPY 



(i9)te#*nfl*jRiT*»«tl§l 
(43) Bie^iws 

2005 *E7 M 28 B (28.07.2005) 




PCT 



(io) ml®'J±mm^ 
WO 2005/069001 Al 



(51) 


§IB*#i*#SI 7 : 


G01N 33/53, 37/00 


(30) 


(21) 




PCT/JP2004/014285 




(22) 




2004 *P 9 M 22 B (2Z09.2004) 




(25) 




B*l§ 


(71) 


(26) 




B*a§ 





Sfclf-T-*: 
$$1112003-333363 
**JS|2003-336771 
$#612003-336793 



2003 *F9 R 25 B (25.09.2003) JP 
2003 ^9 ^ 29 B (29.09.2003) JP 
2003 *£9 £ 29 B (29.09.2003) JP 



(TOYAMA PREFECTURE) [JP/JP]; T 9308501 *M\U)% 
SllJrrJ$Ti®fi*i 1 § 7 •«§■ Toyama (JP). 



= (54) Title: MICROWELL ARRAY CHIP AND ITS MANUFACTURING METHOD 
= (54) fZWOZfr: ^P^xiUTL^^^&tf 



1 (A) 



5 (B) 




(57) Abstract: A microwell array chip comprising microwclls in one 
major surface of a substrate. Each microwell has such a shape and di- 
mensions that it contains only one living cell. On the major surface of 
the substrate where the openings of the microwells are provided, mark- 
ers for the microwells are provided. Another microwell array chip com- 
prising microwells in one major surface of a substrate. Each microwell 
has such a shape and dimensions that it contains only one living cell. 
A projection portion narrowing the opening of each microwell is dis- 
posed in the opening. A method for manufacturing the microwell array 
chip comprises a step of forming a film at least on one major surface 
of a substrate, a step of applying a resist to the formed film, a step of 
exposing the resist surface through a mask having a microwell pattern 
and removing the uncured portion of the resist, a step of making a hole 
of microwell array shape by etching the film and the exposed portion 
of the substrate, and a step of removing the resist Further, another mi- 
crowell array chip of a silicon having microwells in each of which one 
living cell of a subject is contained. Each microwell has such a shape 
and dimensions that it contains only one living cell. 



(c) 



ON 

o 



(57) g«J: &fc<D-j5<D±m;m\Z&&m<DV'( tn^^frZm 

mm±iz ^ ^^poi jkd-7— % — £*rr &v -r o a ^ x ;ut 
*u Btrieve p^xju*. lo^^^^p^iiucioo) 

?<Dm&75&o mm.<D'j>K< tt-yj<D3iWimizm$:r*j&-?z> 

x h®lcv^p^xJU/N*->£^t-£vx££rtLTS3fc 




WO 2005/069001 Al IIIIIIIIIIIIIIIIIIIIIIIIIIHIIUIIIIIIIIl 



(71) UKAfccfctf 

(72) » □ jg (MURAGUCffl, Atsushi) [JP/JP]; T 
9300001 SUJiimUJrfi^tiDr 1 -1 0 8-1 30 1 
Toyama (JP). £ (KISHI, Hiroyuki) [JP/JP]; T 
9300884 gllj!lSllJTfiS*l3fcl£fflT 2 5 5 6-4- 

3-101 Toyama (JP). ft ft; #SS (TOKIMITSU, 
Yoshiharu) [JP/JP]; =f 9398261 gOlftSllJrli&jf 

552-1 r^r7'J>M306f Toyama (JP). jft 
M fef (KONDO, Sachiko) [JP/JP]; T 9300884 g 
LUmSUUmES^fiBr2 5 56-4-3-103 
Toyama (JP). 

(72) &IJB#; fc<fctf 

(75) f§B^%/tBilAr^lll-^tNT(D^;: /Jx« IS (OBATA, 
Tsutomu) [JP/JP]; t 9330981 Sllj^SPgm — ±Hl 
1 5 O Slljmx!B&ii«j-IZ>*— ft Toyama (JP).jS** 
fifcSfe (FUJIKI, Satoshi) [JP/JP]; T9330981 gLUliiSlE 
rti — -tfflT 1 5 O SlJU!lX^liffi-fe>*--rt Toyama 
(JP). ^illj 85: (YOKOYAMA, Yoshiyuki) [JP/JP]; T 
9330981 SOjiiSISgm — -tfflT 1 5 O glUlftXSIft 
ffi-fe — Toyama (JP). (NABESAWA, 
Hirofumi) [JP/JP]; =r 9330981 SUUSiSIEm — ± &T 
1 5 O ^LiJ!ftXHglSffi-tZ>*— ft Toyama (JP).S# 
*1>l£ (TAKABAYASHI, Sotohiro) [JP/JP]; T9330981 g 

ujmKi5amx±fflri so m\um^iiLffii>>$- 

Toyama (JP). S;E (TANINO, Katsumi) [JP/JP]; 
T 9330981 SOJlRiSrarfiZlJifflr 1 5 O SOJlRX^ft 
ffi-fe > $ — I* Toyama (JP). 



(74) ttmA:m*&m£Aft&m&m-*<<t7*(siKs& 

CO.); T 1040031 m^«B**E^-TB8S7^m 
f§ B *1 t!;i/8Pg Tokyo (JP). 

(81) *!£H^^CDfcl*KiK ^TCOaSCDHrtftiS^ 
RTffi^: AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, 
B W, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, 
DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, HR, HU, 
ID, IL, IN, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, 
LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, MZ, NA, 
NI, NO, NZ, OM, PG, PH, PL, PT, RO, RU, SC, SD, SE, 
SG, SK, SL, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, 
UZ, VC, VN, YU, ZA, ZM, ZW. 

(84) esi^^uiy, 4-T<Dmm<n&&&mtf'zi 

fa): ARIPO (BW, Gil, GM, KE, LS, MW, MZ, NA, SD, 
SL, SZ, TZ, UG, ZM, ZW), 0.-7V7 (AM, AZ, BY, 
KG, KZ, MD, RU, TJ, TM), 3 — P V i\ (AT, BE, BG, 
CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HU, IE, 
IT, LU, MC, NL, PL, PT, RO, SE, SI, SK, TR), OAPI (BF, 
BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, 
TD, TG). 

— m&m&n&n 



1 ^<»±&ni&o>Htfteifoi5frz>teft&tf^%k*m 



WO 2005/069001 PCT/JP2004/014285 

m m m 

V n 5 r i fl* -e # 5 y n ^ ^ n ^ * ;vr W ^ j/ 7- tc gg-f S „ #M „ 

$j 200, ooo y >s<m&Mx.X 3H^b 1M, ftH©#^T^tt$r t 
ltJ;9*ftMU-cv^ (ry ^3«tj||ett*ifej $cif*fi— . mG&aRHF. *0-EE3* 

tfc (i 994^), r^w&i, 1 1 j *fH«^\ sitfflai, aim 
m^mm, a 9 9 5^» 0 *&2oo,ooo«£W5 3^* 

Mm*pizfttE-rzm* <DtftM&&&) v >v<# arrays rtiitt fca>ofc. 

1 



WO 2005/069001 PCT/JP2004/0 14285 

jjfeftM$S&tl%\!Rl&tlT^Z> (Altman JD, Moss PA, Goulder PJ, Barouch DH, 
McHeyzer-Williams MG, Bell Jl, McMichael AJ, Davis MM. Phenotypic analysis 
of antigen-specific T lymphocytes, Science, 274:94-96, 1996) D CCD^fe'C 

(4) «a©<Sv^!SSr^-t-S©K:i^lW^36^5 0 

tbTV^S (Abts H, Emmerich M, Miltenyi S, Radbruch A, Tesch H, CD20 positive 
human B lymphocytes separated with the magnetic sorter (MACS) can be induced 
to proliferation and antibody secretion in vitro. Journal of Immunological 

2 



WO 2005/069001 



PCT/JP2004/014285 



Methods 125:19-28, 1989. ) G 

(0. 00l%^±) tittlT*§, tftllitf^-a-Lfc y :"«#as&Mfc^^5a»fcfl¥*r*- 
^fifcj h lit v * * a*o fc 0 

^ n ? ^/vSr^Efc Lfc^-T ^ n t> x ^7 W ^ y ^SrWfls U y Isst&LWj 

3 



WO 2005/069001 PCT/JP2004/014285 

T-ra 5 raja***)*;: i Lfc„ 

4 



WO 2005/069001 



PCT/JP2004/014285 



* s K»tfc*L-cv^s (i) *fct± (2) tiaic^^nDx/uri/^fy^ 

(4) lOp^V- ^KUR^S"^ !7at/V'©a8c^l 0~1 0 0 0 0 <D$$MX 
&5 (3) {CllBgcCD^^n^/WT 1/^^:7% 

(5) ^-^-^^^^^^^jfsl-^^^^ (1 ) _ ( 4) ©vvf*ta>te 

(6) asteg^&ofcfco^— c&s (i) ~ (5) m^Ttifriz. 

(7) SUtti/Da^ ^JR*Vttt«MB»it?*)S (1) ~ (6) 0DV>T*T/d*Kl|B 

(8) tWB-*vf*n *«/w*; R1W7t^ SSfcoffiH: J; D igR 

5 



WO 2005/069001 



PCT/JP2004/014285 



•CfeS, (1) ~ (8) (DV^Ttl^^lEifeO^^^cz^^^T W^^^o 

^ T3 ^;c/VT W^S/^-efc.S (1) ~ (9) OVN-ftL^ 

tt^7ktt^^^^-rs, (i) ~ do) (D^Tnn)^m^(D-r4 ? n^/v-r 

(12) itulEJSTkte^te. -> !) n ^®^fc«^ y*"^^T*MSr3fri-5 % (11) 

d3) w®L<n>— jj<D^mmz&wcm<W'{ *t»*»/i'&*ru mm^-ft-v? 

(14) atraa^jBifRtt. ^MfcKitb^R^t&iBMpas^w-rs j;5fc 

JBMcSavCV^S (13) jC|Bife©-=r^ ^ p !>x;W7 W^-y^. 

(15) H&|B^jg$|5fc«t 0^jfc£:h/5 HP v^^n^j/HuM^ 
*L«-<#^ft:jjaja^jBiab#5^:#$tffc5 (13) (14) KHB*c<£>^ 
^ # n r> ;c7WT W f- >y -?<> 

6 



WO 2005/069001 PCT/JP2004/0 14285 

(16) mmftisv ny ( &m&±ttwmm-?*>z> (13) ~ (15) <D^-rti 

(17) m&&mzLi9Lf}btiitmifi, mitm, mm. ^mrnmm. &mm& 

fcf±8M&jR"e*>£ (14) ~ (16) (D\i^fhmz.^dM,(D^r^ ^ n^7 ^;VT\^4 

(18) W$L<D'}>t£< i: t>-*oi^iilcJg«:MtSIg, 

Sr-g-tf (13) KiflBtt©^ W t7^^T\<'4?-yZf(DWmi3feo 

(19) 2&Rtfisy=t^ 4tm&t£}-±mmM-e3bZ (IS) fclE^Wr-f ^ a $r 

(20) s«*®mas:^6)^«;«s, KftK. mtm, ^mmmstm, &mm%. 
tcnmmm-v&z (is) *ytr* (19) ^iE«6<^^^Pi>:*/i'Tw^-;y:/ 

*bfctt7tctti!s*sr"^ri-5, (1 3) ~ (20) (D\^-?thmz.%m.<D^'( ? 
(2 2) mmm7k^mma^> v = y*js*fcH7 y*^t*isrirt5x (21) 

7 



WO 2005/069001 



PCT/JP2004/014285 



(2 3) lti(Ovxf ^ot> x; ^ U &^>(?*&=.MZl®<D&Mt#;&#i 
IfrlS-v^f ^n^/WS. 1 o©v^ ^ n ^ x ;Hii 1 otO^Mc^^^^ 

(2 4) TtfrlE-^f ^u-^/Wi, RUSTIC m^:o®{cJ;l9#^;$^5#®#: N 
R b < H: jfiA 1t tt £ £> © 2 o^_b Sr j|a#**:^<ft"T?*> 5.(23) 

(£fB*fe©-^ ^ n ? s ;V7 V-f ^ s> 7° 0 

(2 5) v-f ^ n !)i;vroW^|^lt5l^RoIi^ N -^^n^/v 
\z.$t%h b J; 5 <£>E^<£> 0. 5—2 fg©$&ffl-?fc 9 , fro-v* ^ o £ * 

IS-efe5> (2 3) (2 4) (CfEgc©-^ ^x^TWfy/, 

(26) £#«tf3 y ^^T-fe 9 , mc#^iMj y i^jjtsr i ^^-c^tti-r 3 

fcfeJcfflV^ftS^^o^AT Wf^^^fcS (2 3) ~ (2 5) ©V^i* 

(2 7) ^^P7x;KDW7nc*- ^R^fcraSMbvy = ^RtftfeiR 
^tL"CV>6 (2 3) ~ (2 6) (DV^i a ^^^ia^©^^^o»>ai/^TV'^^5/7 0 o 

(2 8) l.tt©^^ n^^/H^^Lfcl^^^^M^W^^ p ? si/I'd* 6> 
IlIJR$tb5J;5fcfflV>fetl/5 (2 7) tEt©W^n I >x^7W^5'7', 

(29) mn&%cm<D^'C?r2V^/i'&ji-pz>m±\^ mmw^M^^tuv 
^/v&miomtf £5\z.m-}t>Mtmfo®mi&&&-rz. (23) ~ (28) ©vi* 

(3 0 ) gna^TK'ttiH^tt, y =^®*ytfi7y*^ae®*^rr5 x (29) 

^IBife© ^ ^ p r> s ;l/7 l"{*3-*,zf 0 
(3 1) gjS©— ^©^^ffi^^^^n^^/v^-f-S-r^^ p !)x;V7Wf 

8 



WO 2005/069001 



PCT/JP2004/014285 



(3 2)«TSBS|[7ktt«*»*x a y«iS4fc(i7 yitttffi^tts, (3 1) 
tEf ©-7^ ^ o i /U7 1/^ f y 

ISIltts 10X1 0 <ot^(^u lb <D Jf^—Zflc*ffl$k'i MT^wntc 

□ ? ^ /i^t w v 7<Dvmjf$k<Dmm m -c *> s , 

H3tt, ixy 3a ilCRlt-v— # — 3d £*-r5^-f * b^x^TM 

fy^ 3a ©YffiB 

07 (A) 2fctf (B) fit, HqgBl 3 af^jglHJW^.L^V^^^ci^^/v 

i z*^ir%T\/j^>yzf(D^mmjBLT*wmmmm'zibz> 0 m7 (ck (d) x 

U (E) tt % N'-r^n^^/H 3<^HPgpi 3 a dill 2' Hp-C^fifcStbS 

08 (A). (B) at* (C) tt N |U7 kteW}<DM&<D*&m<D$g=L<DWim<D'? 

n^x;H3<o|pai3aWi^l2' ' ttS^jggB 1 4 ' 

El 9 (A), (B) (C) tt^yaySfi^fc^^n^x/l/TWfy 

9 



WO 2005/069001 PCT/JP2004/014285 

(D) £>W ? n t7 ^MijjJ&X-hV „ (E) Ov^^n^i/K^i 

mi 2fi. »j4 fc&ftz f7^/vfo\zL?xixi2>— -mi/m^-tz^^ # u $ 

HIl 5te. Ill 4^U/c^^^ci V^frT\s^^iyZf<DlfeW35fe<Dm.WmX« 

& •So 

in i 7 « % ^i^j 6 iz&i^xftmfc^ffifcmm&M ^t^4 tup ^/vco^t± 

^Mx&% 0 

10 



WO 2005/069001 



PCT/JP2004/014285 



? n i> ce^T W ^ y ? vt $ ^;v<dM P t m~ (OW0.0M±\^^ ? 

btlTV^^ fcjWJSUV\ %— ©If O ^ a i> x/l/7 1/^ f y / t* 

Ull^s 10X1 0©-7^^at?x;Hb©^/V-7*lc Irlt3if 
oiattfe-r^ ^ ci t7^J\sT Ujf-yJ' la ©^MS^-To tLT, #10X10 

EPfctatt h xmmx% £ t t>n?# 5„ 

ttfcV^ 10~1 00 00©|§iT'fe5Ci:^5 o 

11 



WO 2005/069001 



PCT/JP2004/014285 



^tfcot^iv^ ^^^^(D-^w- ^igv^^ i-e#^/w— 

OFPR-800 UV\ 

nkmz.£z>Mm$!&mttd:^x< z> 0 



12 



WO 2005/069001 



PCT/JP2004/014285 



mfc(Wx.}-£, w.&#, Afttm), rn^mm, mnmm m^mm, 
&wftm^ mzLftmm, m^nm^ -tftsi±<Dm&%mm mx*&%~th 

z.thx*%z> 0 rm?f^ u^m^s -^4 ? * V ^^(omnfemig, wit 

*&^bJ:5 ii-§^#:^PlJiS©ES^ 0.5—2 fe(D^M, b< too. 8~l.9{g© 
<DWM.<D 0. 5-4 m&mm. 0*L<teO.8~1.9fgtf>f6H x J: b< }i0.8 



13 



WO 2005/069001 



PCT/JP2004/014285 



S„ ^^fi, m%.t£. 3~100|£mt?&5ii:*s-e# % MlS^Byy/-? 

^^b#V>#^^500i@-efe5 iVN^m^fes lcm 2 ^fct9, M*.t£. 2,000 

~l,ooo,ooofl©ttffl-T?*>«ca:^^#s. 

9 tfttnfc: *»Jisptt"C*> 5 £. LV\ *®©Hfldi©ffi^tt, 0~1.0 Sl^n^ 

<©$5ffl^fcSwt^-t?^ % #*L<J4 % 0-0.5 5 ^u^^ffl, J; >9 £f £ b < ii 
0~0. U^n ^©fl&H^fcSo 

fc«SIH4SrW-Jp-r5it*s-Ct*o fllfcrf, ^^A!) P#i£^, «9Jtliil$ 0.5 
~ 1 $?v^<D$ZM*ftWtZZ.bX\ ^^^{-Ao^:»Sr^[^^Jfgtufc < 

<tsci:^Rri6T?*)5 0 fc*3 % ^©m-©^#M^-rSo * 

^^•©aes*, ^jx^^-^^ais xyf^^iiftt, MstiR-rs- 

14 



WO 2005/069001 



PCT/JP2004/014285 



b&X»%& 0 Mx.it s STStfc Multiplex ASE ^ s/^-^^^g^r^V^T^-f ^ n 

ft 5 £ b&X*%Z> 0 

S T Stfc Multiplex ASE ^ s/^-V^g&r/BV^TW 9 n £ 

.X'foSo ^J^.«HtraZ&OSTStt Multiplex ASExyf y^gf |cj;ot> ^j&£r 

5 r t -e^^j^-r s r b $ Q 

15 



WO 2005/069001 



PCT/JP2004/014285 



±mmmt tta, ^y-f^ ^y^u^, mt^=-/^ ^u/ 

<l)**£ttJt (fc: Mtkfofc OFPR-800) *W =2>W&L<D—Jj<D3EMm 

\z&m-tz>o &ytwwte, MMj&ik ofpr-800 swtDttn-e&ox-b^ mmytzw. 

AZP1350 *if-Ct>ftffi-C#5 o 

*3SH4«:^l_h**S/t2e>tJ:ii5ia (fciitf 180*0 K=.^^*KffiSrfr5 = 

^Sr^U teffl (100°C^T) "C^— K=J"^«rff5. W^n^i;w^-y 

16 



WO 2005/069001 



PCT/JP2004/014285 



(2) ^yfy^jx. tf B^M^tt^ y ^ >- Sr^r-f - 57^*y ^^fc^ u , 

(3) 7* h y y ^7 7^ laot-r'f ^ n !?i/W^-yMt5,^ ^ n 17 
(5)7* h l/v>x hfij«/£<*?3rffl^-t, 7* h hSrJftt»l»<o 

17 



WO 2005/069001 



PCT/JP2004/014285 



mfcmzmvxm'jtmfeirzz t&x%^ wz.t£. 100 ,im~immtn: 



18 



WO 2005/069001 



PCT/JP2004/014285 



(1) mki/V =^32a«^$tbfc^y 3>-&K32b (01 5 (A)) £ % 
(f^Mftll (**) y^7y^ffiW^l7^M/^F OFPR-800(32c)$r 
M^U t^^ P! )x;W^- ^32d %T&&.-tZ>o ^<Dm, ^P!?x;^^ 
— ^i: t t>^^60i^7ktt^^Ktt6fcfecD^^-^ 32e 

(Hll 5 (B)) c 

(2) y^m^tiz.x^x^^->^hmmvtc.m<t^v =^^m 32a 

(IU1 5 (C)K ^IfcjSfC7^-hV^ h32c(4^*-f-5 0 ^y^^^^^-r 

n ->rc/^32f -Z)mj$.&tL, m&?\^?>-> 32e &ftf&L,tc.m$-te, i^ttWi- 
5^y 3^g®;5S»ffiU ^CDj»7k'I±^32g^^$tl/5 (Hll 5 (D)) 0 

(3) h b&'&vm< k^4? u?=c/u&&v)ffi-te£ 5(e:->y = 
5 (015 (E))„ 

#-5„ £tT> ^:<DX 5 ^ n >)x;V7W^f y7"©#S*feO- HI 1 

(i) BMbS'y =*^m42a &j&j&£initisv =*>mm*2b mie (a)) ^ n m*. 

19 



WO 2005/069001 



PCT/JP2004/014285 



t£MMJ&tt,JL%£ (tfc) Srf^iyfffim&tfitM-?* h Y OFPR-800 (42c) £ 

Mtt\^Mtfi<Dm7k&mi&&WLi?Z>tclt><Ds<?-- ls42e &Mi$^~Z> (M 1 6 (B)) Q 

(2) -7 -ymz b*\z.£vxs<?—i/fabmmvt£m<{ki'y =x^42a &&<9m%, 
i/v ='>$:mtii£ j &z> (mi 6 (c)) 0 n ^ x, v^fcA^* m^*** bzwiy b& 

<o 

(3) t> 5— %M^V ^^Wmm±.\~-7* rVi>* h*W*5\^s v^^n?i/v 
^-y42d ?r^t5 (HIl 6 (D)) 0 tifcs<& — V Mlti Vtcmfcis 

5 (mi 6 (e)) 0 

5 (016 (F)) 0 

J&£tbZ>7 ymffim^, 7 a n y a y^B^^flf 5 i i ^T*t 5„ 

m^Tk^j *m u^tf xmz «t o rts: ^ s ^ £ a* x # . * -r ^ ^ ^ h &u 

^ 7 s W =t — T ^ ^ ffefc J; o x is: if 5 - £ & X # 5 o * , tfffEiWTktti^te; 

20 



WO 2005/069001 



PCT/JP2004/014285 



— £^t*LT&tH^3;-?PJ^-r5C: t/OSpflgtci^So *r£TN £:f&tt# 

ftrlE^SBte. S^^^fgtt btifcM^fulBM p§Pic^mi-§ <£ 5 

l^7<E> (A) (B) S^l l©flt|gl 2/&Sg§:ttb*K 

21 



WO 2005/069001 



PCT/JP2004/014285 



^frbfcttlsT^ m7<D (Ch (D) RTF (E) tt % I«ll©»112' 

mmztxjtnmm-v&Zo w^o!>x;n3©ip§i5i 3 a ^« N j^i 2' <z>- 

t 

HI8<D (A), (B) ^.t^ (C) @7i:l^iJ©IZ©»^^ 
<D (A), (B) Rtf (C) Ji N S^l l©»il2" ^fgjtb^s ££>f^ 
13a Kites mi 2" (D—^X^^fl^mM^l 4' ^^ftt So mi&lftl 4' 

*^ti§|p©w, 7 cd (e) tmfty, RMx3b% 0 

£ b khh 9 las. ^ a ? x/v©^^i^5ir©ii©-7^ ^ p 

HI 9 (C) te. _h|2lH7S.tJ«8 i:l^#©^T*$>9, -^-f a ^/WSigM 
MW:X?-&>Z><D\ZttlsX, HI 9 (D) (D-v-T ^ n ^/WS^-^fc*} , m 9 (E) 
O-r-T ? a ^/W2^3t7l^fc5 0 <&U -^-C ^ ci ^^7K^^^te#^iJPSte 

22 



WO 2005/069001 



PCT/JP2004/014285 



A&m$)s m\m&. mnmm m=.n«m. 
mmnmm. rn^mm, m*f*wm, -bftsi±<Dm&ftmm) mx^^^th 

0. 5—2 fg©iH, b < f± 0. 8—1. 9 m&f&m, X t» 0* L < « 0. 8—1. 8 

0. 5—4 ^©g&ffl, b < tt 0. 8-1. 9 £ 9 0 * L < 0. 8 

23 



WO 2005/069001 



PCT/JP2004/014285 



Zb&X&, 4=teffim&B V £?l£L<«, K^tt 4~15j«m-e$? 

ffl^e>#v^-&jcir±*?i5ooffl-efcs b^?m&frt>, lcm'SfctK m*.t£s 2,000 
~i, 000, 000 ®<Dmmx-%> 5 r. £ tfs-e^ s 0 

24 



WO 2005/069001 



PCT/JP2004/014285 



*^c. *fe^®fcilg}-t^ti/fcli«« N fJtH ^-fbJU. ^<fbJR. ^M^MUB, 

^iii Lttt, mz-u, tjv^— ^ #3, 

3£tR*ffiH:|H!ltb*uSIR©l?^tt, #(-fi!>Jimte&v^ lOOnm d^fc 5 

MmOO^ffl-efc-So £?3:U<te, 300nmd^b l^m(D|@HT'fc^>o 

25 



WO 2005/069001 



PCT/JP2004/014285 



26 



WO 2005/069001 PCT/JP2004/014285 

(1) ^Lfc^!)aySt*I±I^CVD, CVD^©»J;oXift 

(2) 7£j&Ufc*ffil<£>Jtfc:. h«r^i-S 0 

(3) h®|^^P!)i/W^-y^tt5^^^LtI)feU 
Vi?^ ho^«fls*|5^Sr^*i-5. gp^», Z7* hV y^77^iaD, flit 

*Sft&. tr-v?"*?^ T/^y^y^:^** (fctjtfcf. TMAH : 

27 



WO 2005/069001 



PCT/JP2004/014285 



(2) ^Lfc*K©±t7i- hui?x h&t&fiTZo 

(1) L,-ttmm&®L±i^ mm, h^ti^mn^mm, *>z^t*wm& 

(2) &i&\s1tm&<D±K7*bi'i?xh&&l6lr& 0 

(3) 7* b f®ic^^n>>x;w^-y^ft57t h b 

28 



WO 2005/069001 



PCT/JP2004/014285 



(5) mu^m^mmtmntth^nmm.T^m^m=F^iy^^ 

(6) 7* hUi/X h%$Lym< m~<DMm(D^r^^u^^/UTU^^^y 

( 1 ) ffiftvtciy ]) =* ymm±\^.mmit, m cvd, cvd rn^rn^. £ o 

(2) ^^tmm<D±\^^ 7JrY Ui?X h&W?ft1rZ, 0 

(3) 7* V U*J* VWz.-^'t ? n^x/WN'^-y^ft^vx^Sr^tt UV 

So 7* h hf*^*-r§ 0 

(i) v-y=t^s«jb^ cvd, ««cbnftt3R<ip % ^^^^ir* % m^mmm^ 

29 



WO 2005/069001 



PCT/JP2004/014285 



(2) &j&V1tnm<?>±kz. > 7tb^h?rMt5 0 

(3) 7tfW^ Mlcv^ !>i;w^-y^tt5-7^^ ^LT UV 
-ffcJ:?K Wti&±\z~*<f ftt &^/Us*?~ is]) = 

M-tZ>Wi&}%, is]) =t^^y?-l/Jf\^X, — ^A^xyfy^t^V^j/ 

<5 0 

(1) gfe^Ufc^y nyi^c^ CVD, mm, 74 yifisytzHfDjjmz-J: 

(2) mi&^fzMWk^z.? * V UiSx h&MJ5-tZ> 0 -7* h\si?*Ym\z.^s( 

n 7x;w^-y|r^i t§ ^ Lt l)V 7 1 h Ui?x h<D?£m4b& 

30 



WO 2005/069001 



PCT/JP2004/014285 



(1) ^tfc^ynygtit^ CVD. x/<y#mmm<Djjmz£ t) s SMfc 

(2) ^Lfc^cD_b(3l, :7* M^^^h^^i~5 0 

(3) 7* h U*JX. hStv-f ^ P^xyW^-y^ffSv^^^U-C UV 

it^u 7* m^s?* b<D^mkn$-%m3z-tz> 0 7* hy 7797 

=z-y^l/?te, m*-t£, T;vt>y ^vJ-^sfmm {mk.tZ, TMAHitrh^^vV 
Tis^=-7 J*/^ K^-Y FJteif) */Bwtfr5w£asT»#5 0 -tf>f$> 

31 



WO 2005/069001 



PCT/JP2004/014285 



(1) gfe^ufc^y ^^wsl±\z.^ 7^hv^f^Mt5 5 

-7* h v>Jx h<D^mi\^tt*^3zirZ> 0 irt£fr>ib,-7* V V y y*^y-r te:«fc 9 % 

(2) isir^tt, «m$u 4^^n%^^£^<z>^m^xox, ->y=t- 

(3) ^/K^s^^f^ ^tjx.^ T^y^ivy^v^^ TMAH : 

32 



WO 2005/069001 



PCT/JP2004/014285 



(4) itLtC«J;«9, ir©Hi©v<f ^x;i/71/^y^#f,n5, 

m*.t£. RHIffeSii^f, RlW^^fc, 1»»®{£«3; 9*/^fc£;fr.<5# 
®^£(M;u^. A^ft, a*s*£^k i^wi^ m^mm m^ftmm, 

WmftMr^ &7^$t^ ^&U±(DT&&ftWm ftfc5rH 

t? * ft b - o^_b ma.^t> tfcfttfc s r £ t -e# 5 0 M 

33 



WO 2005/069001 



PCT/JP2004/014285 



1 o©^f ^ n !)x;Hc 1 o©4«fflia^M^5 J: 5 KH-Sfc&Mte, M 
♦MftLJ: 5 £f 5£#^JS<Djl^<£>0.5~2fl£<E>fSffl % b < tt0.8~1.9fflFO 

SSffl, j; «? & £ u < « o. 8~i. s fgof&ig-efos r i assays 

©It© 0. 5~4 ^©®ffl N L < «: 0. 8— 1. 9 m<Dmm, X <9 KIJ0.8 

~i.8fe<Di&mx'hzz.kj!>m%X'bz> 0 

-i^t, &#faJIS#By J"«J$©$§£\ £?;£U<te. ift^tt 4~15jtm-e*> 

34 



WO 2005/069001 



PCT/JP2004/014285 



1 oC^^n^iA-TWfy^ttS^^n^^Su, #«JP& 

r±fcv^s % y i/^^^ Sljdkwsw y io B ^ 1 

mfrb&^m&w-zm boo m-e&z> 5 m&frtb, icm 2 ii7c^ mz.t£* 2,000 

~l, 000, 000 <B©«6BBT?*>* i a*-e# 5. 

y ^i^fes^-e, =>yiwi 
imttmitisv =*w&m£fix\,*&z.k&^ f-v^m^m^^ moss 

4l»©M«if^5i^^5 o tot, ift^payitt, fyy^ 

35 



WO 2005/069001 



PCT/JP2004/014285 



(D^h 5 Z t mi* b < ^ ct >7 x;V7 W ^ j/ ^© * a /USUI*©*® fit % 

SrftJRU !>^^[^§Pfc{t^jl^{^^Bn^7-7K^J^^fc{«^vy = ;/j3il£r 

36 



WO 2005/069001 



PCT/JP2004/014285 



fe«foW^O!>i;V7 Kfy/W 9*->!7 r7^/H*I 

37 



WO 2005/069001 



PCT/JP2004/014285 



^a/vr wr^y^fc^T, -e^f ^ o i> 3i/n^®Sr 7 n n # — 7$ ^m'VWOt'f' 

miit. is V =» if <£>^£_k® la tc#H8fc©^^r ^ n £ 31 lb tf*^ £ 

fc"t-«/tJe>Kl3a^*Sfc (fciifll 0X10:100*-) W4SLt*9 7*9~- lc 

38 



WO 2005/069001 



PCT/JP2004/014285 



^-^-(OftMft&te&TCOmy (0 2) -CfcSo 

^^Sr 2 il «9 ^-Tc 
-^-tf-fEMs (i) 

(DmitisV =*^m2a ^)0V^fcv'y = ^Kf£2b (HI2 (I) (A)) fc-wfcHsiase 

^bxn («) /tfvyfmmmtfvm?* hut?* h ofpr-soo ^m^i^ 
is 2c *&m-tfcmi&-tz> (®2 (i) (b)) 0 

(3)^5—^. 7* hV^ b 2d£^LTW^n^/p&{^a^5fc£>^i& 
^ftMn^*-^2e 2b ±{z:^i-^ (El 2 ( I)(C).&t*(D)) 0 

?~sl<2f ZftMlrZ (0 2 (I) (E)) 0 

(6) (3)-e»byt7^- h h 2d /k rir h ^-eix!? m— 

(Dffi>M<D-?4 lyVTWfj'^ifc (0 2 (I) (F)) 0 

^-#~«2£c(II) 

(1) BMbfU =x^]0|2a ©OV^^D =^S*£2b (02 (I I) (A)) 
^JS'fbXll (WO >7^M^l7t h VS?* h OFPR-SOO Sr^fiJU ^ 
-^^^->-2c^^±(^^-r5 (0 2 (II) (B)) c 

(2) m®mftb*\Z.£Z>7* hUi?X b<DMm&®ifa±<D%bfc s 1 80tl?3O^ 

39 



i 



WO 2005/069001 



PCT/JP2004/014285 



(3) t> 5— Sx7* h Wv 5 ^ h 2d'4rjfe^JUTW^n i^aiyv/Srf^Jjl-^sfcfciEljK 
5SfcP§n^* — ^2e Sr^y 3^3HR2b ±fc»jat5(H2 (I I)(C)^(D)) 0 
C co £ # , iM^^felfi loo~no < Cm^©|£M-e=fT 5 o 

(4) 7yHfeT?winS5©ifcfls'>y = >jR2a &&t>i&t, ->y (HI 

2(11) (E». 

(6) i^y = 2b JiOBMb^ y 3^ 2a t Lt s K^-T^y^^^ 

t5i bte£ 9, Jg— ©ffifilo-r-f ^ n ^/VT WT-s^Srfafc (0 2 (I I) 
(F)) e 

2 

(Mit-^-^-) 

EI 3 ttixy a 3a Jn^(aa^^Ur-?:OmSL3fe5r_blEIII#^®m^ 

— J; o r«j£T?HBte-*-5SI*-^— # — 3d co USS^r fe5„ V 

40 



WO 2005/069001 



PCT/JP2004/014285 



tx^ &ftmmy£*w&xft J B£M£i£Mmmw:^mA'rz> ^. txt^m^m^ 

It UWJftT? # S ± 5 fc: * 6 o 
jaja3fe*^^tfcSLS*5iV>5*^br±, Hfl^4b i^fc°^5: y 

> t bfc^^ov^x. hi 5 ^ 6 \z&<!^xm.m-rz>o 

(Dlfe-fb^y 3^J8l5a oov>fc^y =^3&K5b (05 (a)) fciWfctfJKjftjSfl: 

It (80 y#9y^«MB5RaK^S!7* h h OFPR-800 (5c) U ^ 

— ^5dSr3£*i±^fifti-S (EI 5 (B)) 0 
(2)7yii:iot7t r-W?* h5c^bPP L-cv>5^fb^y ayjftsaSrl&lJ 
<D^%^ isV 3>-^r^W$ii:-5 (0 5 (C)), 

^%*5rfrv\ Da^fllJftSeSrfm-t** (05 (D))„ i©^-C*»WJC,fc©^ 

(4) ir-cm^tft^ y =« ^jr^mss/ y = i/m&o^xtmm&mm 
mmBbmmtemnmi&irz me (a)). 

41 



WO 2005/069001 PCT/JP2004/0 14285 

(5) nTf7* h V 5f trMLt (0 6 (B)K ^^n!>x;WN^-y 5g 
fr*)m%*yV =*ls'*mtii&&Z> (06 (C)) 0 

(6) ^g(u)!Si:-C7t Y\si?* h 5f ZmymZs K7^x y fy^ r^m-, 
S>^J/^J;oTW^tt^/l'5h&fi^H-& (0 6 (D)) 0 

(7) j&g#5fe;frtf, 7^- hl/^* f> 5f £r$t«9l&#> ^-O^O-^-f^ uS^/v 
TKfy^^ffc (0 6 (E)) Q 

«F>|3 (Jfc^H^M) 

mMisfDmvims&tiitmmx^Zo (100) m->v =*>Mfoiimm±\zm}& 

? n ? 13 H Pt, i ^ n ^~^C+5 ^ n >-e£> 

5 0 •>a:^^$tL-CV^^V^*®«^bl^^ ^JS^O^S 12' ^fc^T 

V^o &fc*^V^>'y-FZ>Z-bX«Ml&£tlZ>t~/l'(DMa1® 13a *MJ1 
12' i£<£5J!£^<D^g|S 14 aSfrJiU-CV^o itJUIJa 12' <7)ff^^, |It/^ 
-^-^b^C5^^VT^^^»$tb-CV^^ 0 ^m«12' 
Siffi^O^SU 14tt^-r^n^ai/H3 ^r3i5/^^^^i-§^^ x 12' 
^fc^^^^^-f^o, M^LT^MIJl 12' ©T^T'^^^y 

(1) (10 0) S/ V = f2&K 1 1 SrSftifcfls U ^M^-lfcju m gSoi^l 12 £r7£ 
^t5. C0 9 (A)] 

42 



WO 2005/069001 



PCT/JP2004/014285 



(.2)7* h V y^7 7^Itlut, — >■ 15 ^VP =r^3E*E 11 

•>*/i^fP^o^U a^Sratm***, [0 9 (B)] 

(s)^ciMbif- hy^^/vr^^^ATK^ (9 0°c. 25%) «wn % ->y=t>;^ 

fcJ!K©^#$ wfcJ;oX*S$ti/5. [0 8 (B) ] 

IZOii©v^ a !>x/VT Wf y^tts HI 9 (D) RX$ (E) <Dffi 
J&<D4*-e*>oTt>«tV\ 0 9 (D) (E) ©#3tO-^>f 

00*.*^ i^y 3V3&KSr3B*lbyt»^, 09 (D) RIE K^-fxy^i'^ 

(10 0) ^ (110), (111) EiU IWCtLtil/ixy 
^^^ffi^^SJ;5'&^^-^^Sr3B^i-5r.fc"t?Rr«i"Tf*>S. HI 9 (E) 

So 

43 



WO 2005/069001 



PCT/JP2004/014285 



y 10 4 ~10 5 « (10 4 ~10 5 cells//*l) JSTOtt^ 

#-T5fcJ?)^, HBSS(Hanks' balanced salt solution) i^AilXiS < „ 

2. ^IIM&^^£<Ht5o S'J^^ffii-S^^^r-y^ (DM! 

jg^ft (532nm) MM LTf)fe^|gt5 CellTracker Orange ^-feS:?? 5 <, 

5. ?-y^±(D 4500 ?:n/v£31$RU -?:©5%^^U-CV>5'>^/K^#: 
Irti5 0 TW§£ (;fcf*#0 {4^T^S:r^m-r5o 
TW^ OfcSW = (^ft£^bTV^?cr:^|j|5:/4500) X 100 



44 



WO 2005/069001 PCT/JP2004/014285 

*1 





d 


P 


2r 


Wl 


W2 


rw mm) m 




9. 2jum 


13. Ojurn 


12/im 


0. 5/2 m 


2. 7j*m 


—73% 




11. 8/2 m 


16. 7 ju m 


13. 9/zm 


1. 4/zm 


5. 0/zm 


—24. 9% 



&*5. TW *^<Z>^£;am^^ft±.-f-5#!, -f^^B 

So 

^ WJ 4 

( -y n # - # >m&&mmM) 

# ? x (i % CxFy J: o X3&$t £ fife >m 21c j^j^fifc 

tJS'JJ 3^**ffi21d l£i4##LfcV\, rtbfdioT, T-f ^ a 21b 

45 



WO 2005/069001 PCT/JP2004/014285 

r. 

=^|K 22a 3jS^J***bfe'>y a^jK 22b fcl, 0SitW!3fcgCJ5S^X^| 
(ttc) /#9y^«Ji5RaK^S[7* h h OFPR-800 (22c) SrJfcft U v>f 

n^/w^-y 22d ^©it^MoMltltJ: 9 ( 1 

ooHiioics^) tff5, 

AtSrttioT, U = ^3&K 22b Sraiy^l^U^f *n •>a:/V22e £r?£ 
(4) SI^ & % 5 ffl LfcSftSr, ^ ^ y -/vtfcttTt b y<t if©t«i©ill ta» 

46 



WO 2005/069001 



PCT/JP2004/014285 



2. fttttftfl (10~30 ©<>x^l^ T^T ^ n-^~fc°a.U— ^ 

£>i&) xioo 



Sc2 





A 


B 


c 


D 


E 


F 


rw (as*) * 


99.4% 


99. 2% 


99. 2% 


99. 4% 


99. 3% 


98. 9% 




0% 


10% 


6. 7% 


50% 


30% 


89. 3% 



U-^Mtfl! : ^m/t^ lljtm. ag§ 30Aim 

■f-^/VA-C : =»— ^-f l^fcU ^ mm : 8min 

f-^^D~F : 3— "5V ^y^-ly^nm ' 8min+ = «— 7V ^^H*W : 



lmin 

47 



WO 2005/069001 



PCT/JP2004/0 14285 



mi 3 #&) 

(Dsw&fp =» v 23a »^^^cixy = ^mm 23b ic^-wittfjioscjS'fbxatd*) 

y^yy^tM^^S^ h OFPR-800 iMfcfrU'^'f ^ 
23d Sr^i-«„ 

(2)/7Xv K7^xj/fy^ft SF6 ft^ixy a^y^-l^jtf^Sri&A 
(4) V 5 RCA^-efe5T^=Tgfe#- (T^^T+ii^7K*7R+7k)^ 

ft&tt 10 5 cells/jaLT?feS o 



48 



WO 2005/069001 



PCT/JP2004/014285 



a?3 





A ' 


B 


C 


D 


E 


F 




99.4% 


99.2% 


99.2% 


91. 6% 


98.4% 


98. 5% 




0% 


10% 


6. 7% 


45% 


30% 


55. 6% 



f-fTVWfcfil : t7=c^m Hum m& 30jum 
f">-^A~C : BMfcfllfcU xyf : 8min 

fy^VD^F : ifc-fbfil*) Do ^y^^^M : 8min HfcifiS : 1100<C Bfcfb 
: ftf&mm Wtfc&ffl 30min ^fbJ^J* : 63nm ( 1/ V a >-^f H ® (100) _h) 



mmm 6 

a«Ufcm(-7na^-2l?^^^Ufc„ sp»ft:«ygH:, STS tfc Multiplex 

tfcio-C^Tofec r^ipl-bT. rtffiKli«SO. 5(im© 
QQftiiij^O. 1 ju m ©D!]£ilr^o 2 8g©-7xf ^ n ^ x/i^T V-f f yT'SrM 
Lfco F*3^«£0. 1 j« miDlIlfllr^o ^ n ^ x;i/©tt^I§:i l" 7 

T?USSt*«rfMli Lfc„ 4 t^f". HmvittoffomMti 106ceiy^L 

49 



WO 2005/069001 



PCT/JP2004/0 14285 



*4 











8 0% 


10 0% 




0% 


9 0% 



§13 £r?FM; b tc a STS *± Multiplex ASE ItM ^X^-y^>- ?%)M 

x, Mu^<Dw^m*h^^ ?*v^;v%wm-rz>?Lbfrx%fr 0 mnm~ 

50 



WO 2005/069001 PCT/JP2004/014285 

51 



WO 2005/069001 



PCT/JP2004/014285 



52 



WO 2005/069001 



PCT/JP2004/014285 



» t © I I 

K b tbX V ^ 1 * fc fit 2 fcifBifc© * o V * ;V7 ^ y 

4. lo©^ ^^Mi"^-^^ ^ n ^^/KD^c^ i 0~ 1 0 0 0 oofgffl-efe 

3 If 3 \Z.mWL<D-?4 9 n ? x./VT W y ~fo 

7 . 3£«ri^ 4kJR*fcfi»li3R-cfc5lll^3g l — 6 (D^Ttifr i m^m 
Wu<D^r^ 9 xs ^7^;VT W f- y zf 0 

53 



WO 2005/069001 PCT/JP2004/014285 

£> 5 . w i ~ 8 <d v >-f i ^(dia«co^-r ^ n r> ^ w ^ ? 

i o . tkifcrnm* y wq*-c& ^ . mmm^m v 1 w&ri&m-rsfc 

K15«<^-^ ^ a ^ ^ «/ 

12. MiHj^TK'tt^^s ^^®*fctt^y^^®^^ri-6, st*3fi 

13. ^^^©^^w^-r-r^n^ai^^^-u, Suia^-r ^ a ^ 

/W3\ 1 0©^ ^ p ^x/Wc l o©MJfe©^»^ti5MWi-fe^ 

IS R §15 5i5 Sr^t" 5 -r-f ^ o t> ^ ;VT U-f ^ jy ^ 

14. f&fE^i&SBte, ^«*®}^^^^cJK^MI2MP§P^tH-rSJ:5^ 
J&^tbTV^fiNtill 3M©-7-f^n9x;l/7Wfs'7* 0 

15. itufE^gB^J; 9^$tv6§fiP^±#^fi, ^^^a!>zc/K^#3$tL 

i e. a^as^y ^m^tcummmx-h^m^i 3~i s^w-m^i 
izmmmxh zm^i 4~i 6<D^-rfh^im^m^(D-^^ ^p^x^tk 



WO 2005/069001 



PCT/JP2004/014285 



20. BfeffjK* mum, ^nmmm, &mm-£fc 

feMmmx°& zmmmi SSfcttl 9{cfB*fctf>^-f ^p^a-T \"<*$-vzf<DWt 
fc**tt«*Sr#^"*, fflfefcSl 3-2 0<75V>Ttb*»l«|e:iatt©^^n^* 

2 3. IRafcfiW-r^^o^ai/VSr^rU 4 ? & V ^ Mz. I m<DW?kW-£.WM 

2 4. HulE^-r^n *3i/W± % Rfl!^ J: &«j*£jh,5#®#. iMR 

2 3 R:|BitO^>f^ * !>x^TWfy/, 

55 



WO 2005/069001 PCT/JP2004/014285 

2 6. y ^^-efe «? N y ^x^sr i ^B^-e^m-t-^fc 

#>i£/BV^;fr5^-f ^ n t>^/VTl^-rg : -y7 P -e$>5lt^:^2 3~2 5 (DV^f 6 *!,^ 

*l/rv^ff5j<:]S2 3~2 6 ^>V^tL^l^(C|Btt©^^ ^ v t^/UT Wfy/ 

2 8. lffi<D-*Ji? v ^ai/W^^Ufcl^cD^#:|fflJ^/5S-7^ ^ n ^/l^£>® 

^^sit?Htf £5\z.mibthtcmfc®imm*^-tz>, mm 2 3-2 8<D^-f*u 

3 0. MlS^tt^fi, ^ y n ygl^fctt7 yitf tffi^f MM 
3 1. S^co— ^©^^ffilc-^^r^n^ai/wSr^r-fS^^o^ac/WTW^y 

32. AH&Mctttttttt. e/y =>^®*fctt7^m^-^®^^i-5. MM 

3 1 |C|Bf©W^P!)i;P7Wfy7 , 0 



56 



WO 2005/069001 



PCT/JP2004/014285 



©***©©**©© 
©**coo**oo 
*ooooooo©o 
o**ooo*oo© 
©*©©©©**©© 
©ooooooooo 
©***oo*o©o 
o***o©*o©o 



oooooooooo 
oooooooooo 
oooooooooo 
oooooooooo 
oooooooooo 

©OOOOOOOOO 

0000*00000 
00**0000*© 



© © © © © 
* ♦ ♦ 



♦ * 

oooooooooo 

**©©©©©©©© 
*©©©©©ooo© 

OOOOOOOOOO 
OOOOOOOOOO 



* * * o * * * 
© * o o * o o 

* * o o * © o 
ooooooo 
o o o o o o o 

0 * 0 0 0 0 0 

© © © O O 

o * o o * © ♦ 

© © o o o * o 
0*000*0 



* * 

* * 

* o 



© © * © 



• ooooooooo 

000*00**0* 
OOOOOOOOOO 

00****0000 

OOOOOOOOOO 

*o****oooo 

OOOOOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 
OOOOO OOOOO 



* O * * o 



© * * 



00*0000000 
0*0*000000 
0**0000000 



o o o © o 



* * © * * « 

* o o o * * 



ooooooooo 

00000*000 



OOOOOOOOOO 
000*000000 
OOOOOOOOOO 
OOOOOOOOOO 

OOOOOOOOOO 
OOOOOOOOOO 

OOOOOOOOOO 
000000**0© 




* © © © © 



o © 

© © 
© © 



© o © 
* * * 



o © 
© o 
© © 



* * * * © * * 
©©***©* 



****** 
© o o * o © 



* o o 

* © © 



1a 



-1b 



1/16 



WO 2005/069001 



PCT/JP2004/014285 




2/16 



WO 2005/069001 PCT/JP2004/0 14285 



02 (n) 

2a 




3/16 



WO 2005/069001 



PCT/JP2004/014285 



1213 



oooooooooo 
oooooooooo 

OOOOOOOOOO 

tooooooooo 

OOOOOOOOOO 

oooooooooo 
oooooooooo 

oooooooooo 
oooooooooo 



oooooooooo 
0000000006 
oooooooooo 
oooooooooo 
oooooooooo 
oooooooooo 

OOOOOOOOOO 
OOOOOOOOOO 

oooooooo 



0000000600 

0000000066 

0000000060 

oooooooooo 
ooooooooo 

OOOOOOOOOO 

oooooooooo 
oooooooooo 




ooooooooo 
ooooooooo 
ooooooooo 



6000000000 



oooooooooo 
oooooooooo 

OOOOOOOOOO 

oooooooooo 



oooooooooo 

OOOOOOOOOO 

oooooooooo 



oooooooooo 
oooooooooo 
oooooooooo 



OOOOOOOOOO OOOOOOOOOO 



o o o o o o o 

o o o o o o o 

o o o o o o o 

o o o o o o o 



oooooooo 
oooooooo 
oooooooo 
oooooooo 




3d 



' ES G3 IEI H £H 3e 



\ 



04 



1 



\\// 




4/16 



WO 2005/069001 




(O 



nnnn nnnnn 




5e 



(D) 



5/16 



WO 2005/069001 



PCT/JP2004/014285 




6/16 



WO 2005/069001 



PCT/JP2004/014285 




7/16 



WO 2005/069001 



PCT/JP2004/014285 



M8 




13 



8/16 



WO 2005/069001 



PCT/JP2004/014285 




9/16 



WO 2005/069001 



PCT/JP2004/014285 




1 1 



21b 21c 



o 
o 


o 


6 

O 


o 




f O 



21a 



21 d 




21a 



21d 



10/16 



WO 2005/069001 



PCT/JP2004/014285 




11/16 



WO 2005/069001 



PCT/JP2004/014285 



013 




12/16 



WO 2005/069001 



PCT/JP2004/014285 



mi 4 



/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 



OOOOOOOOOO OOOOOOOOOO ooooooooeo 

OOOOOOOOOO DOOOOOOOOO OOOOOOOOOO 

OOOOOOOOOO OOOOOOOOOO OOOOOOOOOO 

OOOOOOOOOO OOOOOOOOOO OOOOOOOOOO 

OOOOOOOOOO OOOOOOOOOO OOOOOOOOOO 

OOOOOOOOOO OOOOOOOOOO OOOOOOOOOO 

OOOOOOOOOO OOOOOOOOOO OOOOOOOOOO 

OOOOOOOOOO OOOOOOOOOO OOOOOOOOOO 

OOOOOOOOOO OOOOOOOOOO OOOOOOOOOO 

OOOOOOOOOO OOOOOOOOOO OOOOOOOOOO 

OOOOOOOOOO OOOOOOOOOO OOOOOOOOOO 

OOOOOOOOOO OOOOOOOOOO OOOOOOOOOO 

OOOOOOOOOO OOOOOOOOOO OOOOOOOOOO 

OOOOOOOOOO OOOOOOOOOO OOOOOOOOOO 

OOOOOOOOOO OOOOOOOOOO OOOOOOOOOO 

OOOOOOOOOO OOOOOOOOOO OOOOOOOOOO 

OOOOOOOOOO OOOOOOOOOO OOOOOOOOOO 



OOOOOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 
OOO OOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 
OOO OOOOOOO 



OOOOOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 



OOOOOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 
OOOOOOOOOO 




13/16 



WO 2005/069001 



PCT/JP2004/014285 



Ell 5 




14/16 




15/16 



WO 2005/069001 



PCT/JP2004/014285 



mi 7 




EI 1 8 




16/16 



INTERNATIONAL SEARCH REPORT 



A. CLASSIFICATION OF SUBJECT MATTER 

Int. CI 7 G01N33/53, G01N37/00 



International application No. 

PCT/JP2004/014285 



According to International Patent Classification (IPC) or to both national classification and IPC 
B. FIELDS SEARCHED 

Minimum documentation searched (classification system followed by classification symbols) 
Int. CI 7 G01N33/53, G01N37/00 



Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched 
Jitsuyo Shinan Koho 1922-1996 Toroku Jitsuyo Shinan Koho 1994-2005 

Kokai Jitsuyo Shinan Koho 1971-2005 Jitsuyo Shinan Toroku Koho 1996-2005 

Electronic data base consulted during the international search (name of data base and, where practicable, search terms used) 



C. DOCUMENTS CONSIDERED TO BE RELEVANT 



Category* 


Citation of document, with indication, where appropriate, of the relevant passages 


Relevant to claim No. 


Y 
A 


WO 2002/055653 A (Matsushita Electric 
Industrial Co. , Ltd. ) , 
18 July, 2002 (18.07.02), 

& US" 2003-0113833 A & EP 1352952 A 
& CN 1458972 A 


1-12,23-32 
13-22 


Y 
A 


JP 5-240869 A (Suzuki Motor Corp.), 
21 September, 1993 (21.09.93), 
(Family: none) 


1-12,23-32 
13-22 


Y 
A 


JP 63-106565 A (E.I. Du Pont De Nemours & Co.), 
11 May, 1988 (11.05.88) , 
& EP 258565 A 


1-12,23-32 
13-22 


Y 
A 


JP 2003-33177 A (Mitsuo OKANO) , 
04 February, 2003 (04.02.03), 
(Family: none) 


1-12,23-32 
13-22 



a Further documents are listed in the continuation of Box C. 



□ See patent family annex. 



• Special categories of ci ted documents: 

"A" document defining the general state of the art which is not considered 
to be of particular relevance 

"E" earlier application or patent but published on or after the international 
filing date 

"L" document which may throw doubts on priority ctaim(s) or which is 
cited to establish the publication date of another citation or other 
special reason (as specified) 

"O" document referring to an oral disclosure, use, exhibition or other means 
"P" document published prior to the international filing date but later than 
the priority date claimed 



"V later document published after the international filing date or priority 
date and not in conflict with the application but cited to understand 
the principle or theory underlying the invention 

"X* document of particular relevance; the claimed invention cannot be 
considered novel or cannot be considered to involve an inventive 
step when the document is taken alone 

■ Y" document of particular relevance; the claimed invention cannot be 
considered to involve an inventive step when the document is 
combined with one or more other such documents, such combination 
being obvious to a person skilled in the art 
document member of the same patent family 



Date of the actual completion of the international search 
15 March, 2005 (15.03.05) 


Date of mailing of the international search report 
29 March, 2005 (29.03.05) 


Name and mailing address of the ISA/ 

Japanese Patent Office 


Authorized officer 
Telephone No. 



Form PCT/IS A/2 10 (second sheet) (January 2004) 



mmmm^ pct/jp2oo4/o 14285 



a. &m<om-t%ftm<o$rm. m&¥ftf&m (ipo ) 

Int. C 1 7 GO 1 N3 3/5 3, G01N37/00 



»HE*:*?ofc«/NRjm (BRttl&ttR (IPC) ) 

Int. CI 7 G01N3 3/53, G01N37/00 



B*H3lffiff^^fl 1 922-1 9 9 6^ 

B#B2rRl2IJB?&rS&fc« 1 9 7 1-200 5¥ 

&*mamMfaM&!&i 1994-2005^ 

B*m£:M%TM&M2t¥i 1996-2005^ 



c. 



BarfsfcWft fetus Aft 



HM-S 



Y 
A 

Y 
A 



WO 2 0 0 2/0 5 5 6 5 3 
0 2.0 7.1 8 

& US 2003—0113833 
& EP 1352952 A 
& CN 1458972 A 



A (feTS^l 
A 



2 0 



JP 5-240869 A (;* X^ttSfc^fcfc) 1 9 9 3. 0 9 
2 1 



1-12, 
2 3 — 32 
13 — 22 



1 — 12, 

2 3-32 
13-2 2 



G><] cm<Dm%i^-xmmm£*ix^z„ 



TEj BRttJKBtfr<PtfUH£fcll#VI : -e*>sas % BRUMS 

xsft (a* 



rxj !i#{cM5SwfeSS:iSfc-efc<5T, ^^i^co^-e^K 

Tyj ^t-BBjgwfcs^T-fcoT, ^zSCiSfcitfiioi^ 

•fcoT^t£riS&V>fc#;i fetus to 
r&j p-/N'fyh77;y-M 



1 5. 03. 2005 


mmm*mm* 2Q _ 3 _ 2Q05 


B^H^fF^r (I SA/J P) 
»5{S!## 100-8915 


WW*** (*K*>*5«ft> 

03-3581-1101 F> 


2 J 


9 5 0 7 


3 2 5 1 



»CT/ISA/2 10 («2^) (2004^11) 



B^tt}ffi#-*§- PCT/JP20 04/01 428 5 



C , Oftfe) 



JP 63-106565 A (-f— • T-f • T^/tfV 
T — X • 7y K • =i 1988. 05. 11 

& EP 258565 A 



K • 



JP 2003-33177 A 
0 4 



2 0 0 3. 0 2. 



1-12, 
2 3 — 32 
13-2 2 



1-12, 
2 3-3 2 
13-2 2 



flKPCT/I SA/2 1 0 (&2-i— S?©i6fe#) (2004^1^) 



This Page is Inserted by IFW Indexing and Scanning 
Operations and is not part of the Official Record 

BEST AVAILABLE IMAGES 

Defective images within this document are accurate representations of the original 
documents submitted by the applicant. 

Defects in the images include but are not limited to the items checked: 

□ BLACK BORDERS 

□ IMAGE CUT OFF AT TOP, BOTTOM OR SIDES 

□ FADED TEXT OR DRAWING 

□ BLURRED OR ILLEGIBLE TEXT OR DRAWING 

□ SKEWED/SLANTED IMAGES 
COLOR OR BLACK AND WHITE PHOTOGRAPHS 

□ GRAY SCALE DOCUMENTS 

□ LINES OR MARKS ON ORIGINAL DOCUMENT 

□ REFERENCED) OR EXHIBIT(S) SUBMITTED ARE POOR QUALITY 

□ OTHER: 

IMAGES ARE BEST AVAILABLE COPY. 
As rescanning these documents will not correct the image 
problems checked, please do not report these problems to 
the IFW Image Problem Mailbox.